L-borneol regulates rno-miR-127/ PODXL2 to promote hair follicle stem cells to repair skin wounds

IF 4.7 2区 医学 Q2 IMMUNOLOGY
Zike Liu , Baolin Ye , Haoxiang Ye , Qing Zhong , Jiecheng Kong , Xianxi Zhou , Chunmei Ma , Aijun Liu
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Abstract

Hair follicle stem cells (HFSCs) can quickly activate and migrate to the wound site, differentiating into epidermal stem cells to facilitate early epithelialization. During the wound healing process, microRNAs (miRNAs) function coordinately. Chinese medicine borneol is derived from the Cinnamomum camphora plant, and its principal component, L-borneol, is renowned for its potential in facilitating skin wound healing. However, it remains unclear whether L-borneol can stimulate HFSCs to differentiate into epidermal cells or whether miRNAs are involved in this process. In the current study, HFSCs were isolated from the vibrissae of rats and identified based on the expression of CD34, Integrin-β1 and keratin type 1 cytoskeletal 15(CK15). We observed that stimulation with L-borneol significantly increased the differentiation marker K14 in HFSCs, suggesting that L-borneol could promote the differentiation of HFSCs into basal layer cells. On this basis, we transfected and confirmed that rno-miR-127 inhibitor could promote the differentiation of HFSCs. Furthermore, we demonstrated that PODXL2 is a target gene of rno-miR-127 through dual-luciferase reporter assays and confirmed that the rno-miR-127 mimic could inhibit the expression of PODXL2. To further elucidate the targeting relationship, we constructed the siPODXL2 fragment using siRNA technology, demonstrating that reducing PODXL2 expression can inhibit the differentiation of HFSCs into basal layer cells. Finally, a rat full-thickness skin defect model illustrated L-borneol-mediated negative regulation of PODXL2 by rno-miR-127, promoting skin injury repair through HFSCs.
l -冰片调节rno-miR-127/ PODXL2促进毛囊干细胞修复皮肤创伤
毛囊干细胞(Hair follicle stem cells, HFSCs)能够快速激活并迁移到创面部位,分化为表皮干细胞,促进早期上皮化。在伤口愈合过程中,microRNAs (miRNAs)协同起作用。中药龙脑是从香樟植物中提取的,其主要成分是l -龙脑,以其促进皮肤伤口愈合的潜力而闻名。然而,目前尚不清楚左旋冰片是否能刺激HFSCs向表皮细胞分化,也不清楚mirna是否参与了这一过程。本研究从大鼠触毛中分离出HFSCs,通过CD34、整合素-β1和角蛋白1型细胞骨架15(CK15)的表达进行鉴定。我们观察到,左旋冰片刺激显著增加了HFSCs的分化标志物K14,提示左旋冰片可促进HFSCs向基底层细胞分化。在此基础上,我们转染并证实了rno-miR-127抑制剂能够促进HFSCs的分化。此外,我们通过双荧光素酶报告基因实验证明了PODXL2是rno-miR-127的靶基因,并证实了rno-miR-127模拟物可以抑制PODXL2的表达。为了进一步阐明靶向关系,我们利用siRNA技术构建了siPODXL2片段,证明降低PODXL2的表达可以抑制HFSCs向基底层细胞的分化。最后,大鼠全层皮肤缺损模型表明,l-冰片介导的rno-miR-127对PODXL2的负调控,通过HFSCs促进皮肤损伤修复。
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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